TNF-alpha and IL-6 signals from the bone marrow derived cells are necessary for normal murine liver regeneration.
In the present study, we used bone marrow transplanted mice and revealed the role of bone marrow derived cells in liver regeneration after partial hepatectomy (PH). Irradiated wild type (WT) mice received a bone marrow transplant from either WT, TNF (tumor necrosis factor)-alpha knockout (KO), or interleukin (IL)-6 KO donors. Both TNF-alpha KO- and IL-6 KO-transplanted mice compared with WT-transplanted mice showed decreased hepatocyte DNA synthesis after PH. TNF-alpha KO-transplanted mice showed no nuclear factor kappa B (NF-kappaB) and signal transducer and activator of transcription (STAT) 3 binding after PH, while IL-6 KO-transplanted mice showed NF-kappaB, but not STAT3, binding. Lack of AP-1 or C/EBP binding or expression of c-jun or c-myc mRNA after PH was unrelated to the timing and amount of DNA replication. In conclusion, The TNF-alpha and IL-6 signals from the blood are necessary for liver regeneration and NF-kappaB and STAT3 binding are activated via TNF-alpha and IL-6 signal pathways.
Sudo
Kaori
K
Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
Yamada
Yasuhiro
Y
Saito
Kuniaki
K
Shimizu
Syogo
S
Ohashi
Hazuki
H
Kato
Tomohiro
T
Moriwaki
Hisataka
H
Ito
Hiroyasu
H
Seishima
Mitsuru
M
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology*; D016026:Bone Marrow Transplantation; D006498:Hepatectomy; D020287:In Situ Nick-End Labeling; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D015850:Interleukin-6; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; D014409:Tumor Necrosis Factor-alpha